Cholangitis and Interruptions of Neoadjuvant Chemotherapy Associate with Reduced Overall and Progression-Free Survival in Pancreatic Cancer.

BACKGROUND: Interrupting chemotherapy may explain the reduced overall survival (OS) in patients with pancreatic cancer (PC) with cholangitis. Endoscopic biliary decompression (BD) with metallic stents results in fewer chemotherapy interruptions and a lower cholangitis rate compared with plastic stents. We aimed to determine the impact of cholangitis, neoadjuvant treatment (NAT) interruptions and biliary stent choice on PC patients' survival. METHODS: We conducted a retrospective analysis of 162 patients with cancer of the head of the pancreas undergoing pancreatoduodenectomy after NAT and BD documenting progression-free survival (PFS) and OS. Data on BD, cholangitis, stent type, surgical radicality, and chemotherapy were collected. Survival was estimated based on the Kaplan-Meier method by using the log-rank test and multivariate Cox regression analysis. RESULTS: Median OS and PFS for patients with cholangitis (n = 33, 20%) were 26 and 8 months (95% confidence interval [CI] 20-32 and 5-10 months), respectively, compared with 36 and 17 months (95% CI 31-41 and 12-21 months; p < 0.001 for OS; p = 0.002 for PFS) for patients without cholangitis. Among patients without NAT interruptions median OS and PFS were 35 and 17 months (95% CI 31-40 and 12-21 months), falling to 26 and 7 months (95% CI 18-30 and 5-10 months) among those who experienced an NAT interruption caused by biliary stent failure (n = 26, 16%) (p = 0.039 for OS; p < 0.001 for PFS). We found no difference in OS or PFS between stent types. CONCLUSIONS: Cholangitis and NAT interruptions reduce OS and PFS among PC patients.

Topical pharyngeal anesthesia with articaine for gastroscopy: a double-blinded, randomized cross-over study in healthy volunteers.

OBJECTIVES: The benefits of topical pharyngeal anesthesia for gastroscopy remain under debate. Articaine, a local anesthetic with fast onset and offset of action as well as low systemic toxicity, could be a promising choice for topical anesthesia. The objective of this study was to assess whether topical pharyngeal anesthesia with articaine is beneficial in sedated gastroscopy. MATERIALS AND METHODS: This randomized double-blinded cross-over study included nine volunteers who underwent two gastroscopies under conscious sedation. One was performed with topical pharyngeal anesthesia with articaine and the other with placebo. Hemodynamic parameters including autonomic nervous system state were recorded prior to and during the endoscopic procedure. The endoscopist and the volunteer assessed the endoscopy after the examination. RESULTS: Topical pharyngeal anesthesia with articaine resulted in less discomfort during esophageal intubation and higher patient satisfaction with the procedure. Topical pharyngeal anesthesia with articaine did not increase satisfaction or facilitate the procedure as rated by the endoscopist. There were no clinically relevant differences in hemodynamic parameters. CONCLUSION: The use of articaine for topical pharyngeal anesthesia results in less intubation-related discomfort and better satisfaction.

Endoscopic therapy of sporadic non-ampullary duodenal adenomas, single centre retrospective analysis.

INTRODUCTION: Although sporadic non-ampullary duodenal adenomas (SNADA) are rare, with the risk of progression to cancer, they deserve therapy. Endoscopic therapy of SNADA is effective, but with the increased risk of complications, endotherapy should be performed in high-volume units. The results of endotherapy of SNADA in our unit are presented. PATIENTS AND METHODS: A total of 97 patients with SNADA had endoscopic resection in 2005-2021 and control endoscopies between 3 and 24 months. Snare polypectomy, endoscopic mucosal resection (EMR), endoscopic band ligation (EBL) and endoloop were used (en bloc 37% and piecemeal 63%). In cases of residual/recurrent adenomas, endotherapy was repeated. RESULTS: The median size of the adenoma was 12 (5-60) mm and most polyps were sessile (25%) or flat (65%). Primary endotherapy eradicated adenomas in 57 (59%) cases. Residual and recurrence rates were 24% (n = 23) and 17% (n = 16) with successful endotherapy in 16 (70%) and 13 (81%) patients. Endotherapy was successful in 86 (89%) patients after a median (range) follow-up of 23 (1-166) months. Four out of 11 patients with failed endotherapy had surgery; seven patients were not fit for surgery. There were no disease-specific deaths or carcinoma. Eleven patients (11%) suffered from complications: perforation requiring surgery (n = 1), sepsis (n = 1), postprocedure bleeding (n = 7), cardiac arrest (n = 1) and coronary infarct (n = 1). The thirty-day mortality was zero. Colonoscopy was performed on 67 (69%) patients with neoplastic lesions in 33% patients during follow-up. CONCLUSIONS: Endotherapy of SNADA is effective and safe. Repeat endotherapy in residual and recurrent adenomas is successful. Careful patient selection is mandatory. Abbreviations: ASA: American Society of Anesthesiologist classification; BMI: body mass index; CT: computed tomography; EBL: endoscopic band ligation; EMR: endoscopic mucosal resection; ESD: endoscopic submucosal dissection; ET: endotherapy; FAP: familial adenomatous polyposis; F: female; LST: laterally spreading tumours; M: male; SD: standard deviation; SNADA: sporadic nonampullary duodenal adenoma.

Pancreatic fibrosis, acinar atrophy and chronic inflammation in surgical specimens associated with survival in patients with resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, is increasing in incidence. However, the stromal reaction pathophysiology and its role in PDAC development remain unknown. We, therefore, investigated the potential role of histological chronic pancreatitis findings and chronic inflammation on surgical PDAC specimens and disease-specific survival (DSS). METHODS: Between 2000 and 2016, we retrospectively enrolled 236 PDAC patients treated with curative-intent pancreatic surgery at Helsinki University Hospital. All pancreatic transection margin slides were re-reviewed and histological findings were evaluated applying international guidelines. RESULTS: DSS among patients with no fibrosis, acinar atrophy or chronic inflammation identified on pathology slides was significantly better than DSS among patients with fibrosis, acinar atrophy and chronic inflammation [median survival: 41.8 months, 95% confidence interval (CI) 26.0-57.6 vs. 20.6 months, 95% CI 10.3-30.9; log-rank test p = 0.001]. Multivariate analysis revealed that Ca 19-9 > 37 kU/l [hazard ratio (HR) 1.48, 95% CI 1.02-2.16], lymph node metastases N1-2 (HR 1.71, 95% CI 1.16-2.52), tumor size > 30 mm (HR 1.47, 95% CI 1.04-2.08), the combined effect of fibrosis and acinar atrophy (HR 1.91, 95% CI 1.27-2.88) and the combined effect of fibrosis, acinar atrophy and chronic inflammation (HR 1.63, 95% CI 1.03-2.58) independently served as unfavorable prognostic factors for DSS. However, we observed no significant associations between tumor size (> 30 mm) and the degree of perilobular fibrosis (p = 0.655), intralobular fibrosis (p = 0.587), acinar atrophy (p = 0.584) or chronic inflammation (p = 0.453). CONCLUSIONS: Our results indicate that the pancreatic stroma is associated with PDAC patients' DSS. Additionally, the more severe the fibrosis, acinar atrophy and chronic inflammation, the worse the impact on DSS, thereby warranting further studies investigating stroma-targeted therapies.

Use of self-expandable metallic stents for endoscopic biliary decompression decreases stent complications in pancreatic cancer patients receiving chemotherapy.

BACKGROUND: Both plastic stents and self-expandable metallic stents (SEMSes) are used for endoscopic biliary decompression (BD) among patients with pancreatic cancer (PAC). Cholangitis or stent occlusion often interrupts or ends chemotherapy. We investigated cholangitis, stent occlusion, and chemotherapy interruption rates for SEMSes and plastic stents among patients receiving chemotherapy for PAC. MATERIALS AND METHODS: We retrospectively analyzed data for 293 PAC patients who received a biliary stent at Helsinki University Hospital during 2000-2017. Patients received chemotherapy as palliative treatment (PT: n = 187) or neoadjuvant treatment (NAT: n = 106). Among participants, 229 had a plastic stent (PT: n = 138, NAT: n = 91) and 64 had a SEMS (PT: n = 49, NAT: n = 15). RESULTS: Overall, 15.6% (n = 10) of patients with SEMSes (PT: 20.4%, n = 10, NAT: 0%) and 53.0% (n = 121) of patients with plastic stents (PT: 69.3%, n = 95, NAT: 28.5%, n = 26) experienced one or more stent complications (p < 0.001). Cholangitis developed in 6.3% (n = 8) of PT patients with SEMSes. No patients with SEMSes receiving NAT (n = 15) experienced cholangitis. However, 31.9% (PT: 42.8%, n = 59, p = 0.001; NAT: 15.4%, n = 14, p = 0.211) of patients with plastic stents developed cholangitis. Among all patients receiving NAT or PT, cholangitis interrupted chemotherapy 6 times (9.4%) in SEMS patients and 61 times (26.6%) in plastic stent patients (p = 0.004). Stent occlusion without cholangitis interrupted NAT or PT 2 times (2.1%) in SEMS patients and 31 times (13.5%) in plastic stent patients (p = 0.023). CONCLUSIONS: SEMS is recommended for BD among patients with PAC receiving chemotherapy. Among both PT and NAT patients, patients with SEMS experience a lower stent failure rate, lower rate of cholangitis, and fewer chemotherapy interruptions than patients with plastic stents.

Single-operator peroral pancreatoscopy in the preoperative diagnostics of suspected main duct intraductal papillary mucinous neoplasms: efficacy and novel insights on complications.

BACKGROUND: Distinguishing intraductal papillary mucinous neoplasms (IPMNs) from other pancreatic cystic lesions is essential since IPMNs carry the risk of becoming malignant. Differentiating the main pancreatic duct involving IPMNs (MD-IPMNs) through conventional imaging is deficient. Single-operator peroral pancreatoscopy (SOPP) represents a promising method offering additional information on suspected lesions in the pancreatic main duct (MD). We aimed to determine the role of SOPP in the preoperative diagnostics of suspected MD-IPMNs and identify factors contributing to SOPP-related complications. MATERIALS AND METHODS: In this primarily retrospective study, SOPPs were performed at three high-volume centers on suspected MD-IPMNs. Primary outcome was the clinical impact of SOPP to subsequent patient care. Additionally, we documented post-SOPP complications and analyzed several assumed patient- and procedure-related risk factors. RESULTS: One hundred and one (101) SOPPs were performed. Subsequent clinical management was affected due to the findings in 86 (85%) cases. Surgery was planned for 29 (29%) patients. A condition other than IPMN explaining MD dilatation was found in 28 (28%) cases. In 35 (35%) cases, follow-up with MRI was continued. Post-SOPP pancreatitis occurred in 20 (20%) patients and one of them was fatal. A decrease in odds of post-SOPP pancreatitis was seen as the MD diameter increases (OR 0.714 for 1.0 mm increase in MD diameter, CI 95% 0.514-0.993, p = 0.045). Furthermore, a correlation between lower MD diameter values and higher severity post-SOPP pancreatitis was seen (TJT = 599, SE = 116.6, z = - 2.31; p = 0.020). History of pancreatitis after endoscopic retrograde cholangiopancreatography was a confirmed risk factor for post-SOPP pancreatitis. Conclusions between complications and other risk factors could not be drawn. CONCLUSION: SOPP aids clinical decision-making in suspected MD-IPMNs. Risk for post-SOPP pancreatitis is not negligible compared to non-invasive imaging methods. The risk for pancreatitis decreases as the diameter of the MD increases.

Diagnostic accuracy and interobserver agreement of digital single-operator cholangioscopy for indeterminate biliary strictures.

BACKGROUND AND AIMS: Digital single-operator cholangioscopy (d-SOC) with cholangioscopic biopsy sampling has shown promise in the evaluation of indeterminate biliary strictures. Some studies have suggested higher sensitivity for visual impression compared with biopsy sampling, although assessors were not blinded to previous investigations. We aimed to investigate the diagnostic accuracy and interobserver agreement (IOA) of d-SOC in the visual appraisal of biliary strictures when blinded to additional information. METHODS: A multicenter, international cohort study was performed. Cholangioscopic videos in patients with a known final diagnosis were systematically scored. Pseudonymized videos were reviewed by 19 experts in 2 steps: blinded for patient history and investigations and unblinded. RESULTS: Forty-four high-quality videos were reviewed of 19 benign and 25 malignant strictures. The sensitivity and specificity for the diagnosis of malignancy was 74.2% and 46.9% (blinded) and 72.7% and 62.5% (unblinded). Cholangioscopic certainty of a malignant diagnosis led to overdiagnosis (sensitivity, 90.6%; specificity, 33%), especially if no additional information was provided. The IOA for the presence of malignancy was fair for both assessments (Fleiss' κ = .245 [blinded] and κ = .321 [unblended]). For individual visual features, the IOA ranged from slight to moderate for both assessments (κ = .059-.400 vs κ = .031-.452). CONCLUSIONS: This study showed low sensitivity and specificity for blinded and unblinded d-SOC video appraisal of indeterminate biliary strictures, with considerable interobserver variation. Although reaching a consensus on the optical features of biliary strictures remains important, optimizing visually directed biopsy sampling may be the most important role of cholangioscopy in biliary stricture assessment.

Transpancreatic biliary sphincterotomy versus double guidewire in difficult biliary cannulation: a randomized controlled trial.

BACKGROUND: Difficult biliary cannulation in endoscopic retrograde cholangiopancreatography (ERCP) increases the risk of post-ERCP pancreatitis (PEP). The purpose of this prospective, randomized, multicenter study was to compare two advanced rescue methods, transpancreatic biliary sphincterotomy (TPBS) and a double-guidewire (DGW) technique, in difficult common bile duct (CBD) cannulation. METHODS: Patients with native papilla and planned CBD cannulation were recruited at eight Scandinavian hospitals. An experienced endoscopist attempted CBD cannulation with wire-guided cannulation. If the procedure fulfilled the definition of difficult cannulation and a guidewire entered the pancreatic duct, randomization to either TPBS or to DGW was performed. If the randomized method failed, any method available was performed. The primary end point was the frequency of PEP and the secondary end points included successful cannulation with the randomized method. RESULTS: In total, 1190 patients were recruited and 203 (17.1 %) were randomized according to the study protocol (TPBS 104 and DGW 99). PEP developed in 14/104 patients (13.5 %) in the TPBS group and 16/99 patients (16.2 %) in the DGW group (P = 0.69). No difference existed in PEP severity between the groups. The rate of successful deep biliary cannulation was significantly higher with TPBS (84.6 % [88/104]) than with DGW (69.7 % [69/99]; P = 0.01). CONCLUSIONS: In difficult biliary cannulation, there was no difference in PEP rate between TPBS and DGW techniques. TPBS is a good alternative in cases of difficult cannulation when the guidewire is in the pancreatic duct.

Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2021.

1: ESGE recommends in patients with acute upper gastrointestinal hemorrhage (UGIH) the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Patients with GBS ≤ 1 are at very low risk of rebleeding, mortality within 30 days, or needing hospital-based intervention and can be safely managed as outpatients with outpatient endoscopy.Strong recommendation, moderate quality evidence. 2: ESGE recommends that in patients with acute UGIH who are taking low-dose aspirin as monotherapy for secondary cardiovascular prophylaxis, aspirin should not be interrupted. If for any reason it is interrupted, aspirin should be re-started as soon as possible, preferably within 3-5 days.Strong recommendation, moderate quality evidence. 3: ESGE recommends that following hemodynamic resuscitation, early (≤ 24 hours) upper gastrointestinal (GI) endoscopy should be performed. Strong recommendation, high quality evidence. 4: ESGE does not recommend urgent (≤ 12 hours) upper GI endoscopy since as compared to early endoscopy, patient outcomes are not improved. Strong recommendation, high quality evidence. 5: ESGE recommends for patients with actively bleeding ulcers (FIa, FIb), combination therapy using epinephrine injection plus a second hemostasis modality (contact thermal or mechanical therapy). Strong recommendation, high quality evidence. 6: ESGE recommends for patients with an ulcer with a nonbleeding visible vessel (FIIa), contact or noncontact thermal therapy, mechanical therapy, or injection of a sclerosing agent, each as monotherapy or in combination with epinephrine injection. Strong recommendation, high quality evidence. 7 : ESGE suggests that in patients with persistent bleeding refractory to standard hemostasis modalities, the use of a topical hemostatic spray/powder or cap-mounted clip should be considered. Weak recommendation, low quality evidence. 8: ESGE recommends that for patients with clinical evidence of recurrent peptic ulcer hemorrhage, use of a cap-mounted clip should be considered. In the case of failure of this second attempt at endoscopic hemostasis, transcatheter angiographic embolization (TAE) should be considered. Surgery is indicated when TAE is not locally available or after failed TAE. Strong recommendation, moderate quality evidence. 9: ESGE recommends high dose proton pump inhibitor (PPI) therapy for patients who receive endoscopic hemostasis and for patients with FIIb ulcer stigmata (adherent clot) not treated endoscopically. (A): PPI therapy should be administered as an intravenous bolus followed by continuous infusion (e. g., 80 mg then 8 mg/hour) for 72 hours post endoscopy. (B): High dose PPI therapies given as intravenous bolus dosing (twice-daily) or in oral formulation (twice-daily) can be considered as alternative regimens.Strong recommendation, high quality evidence. 10: ESGE recommends that in patients who require ongoing anticoagulation therapy following acute NVUGIH (e. g., peptic ulcer hemorrhage), anticoagulation should be resumed as soon as the bleeding has been controlled, preferably within or soon after 7 days of the bleeding event, based on thromboembolic risk. The rapid onset of action of direct oral anticoagulants (DOACS), as compared to vitamin K antagonists (VKAs), must be considered in this context.Strong recommendation, low quality evidence.

Repeated Negative Urine Trypsinogen-2 Dipstick Test Rules Out Diagnosis of Post-ERCP Pancreatitis.

BACKGROUND: A dipstick test for urine trypsinogen-2 has been used in the diagnosis of acute pancreatitis, but there are only a few studies exploring the effectiveness of this test for early diagnose of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). GOALS: The authors explore if the rapid point-of-care urine trypsinogen-2 dipstick test can replace assay of amylase in diagnosing PEP. STUDY: For this prospective study, from Helsinki University Hospital 400 ERCP patients were enrolled in whom the authors analyzed plasma amylase or pancreas-specific amylase, bilirubin, and urine trypsinogen-2, and urine trypsinogen-2 with dipstick before, 4 and 24 hours after ERCP. RESULTS: PEP developed in 15 (3.8%) patients. Urine trypsinogen-2 concentrations were significantly higher in PEP than in non-PEP patients 24 hours after ERCP (P=0.001, Mann-Whitney U test) but not 4 hours after ERCP (P=0.094). When combined with abdominal pain symptoms at 4 hours the dipstick test had a sensitivity of 60%, a specificity of 99%, a positive predictive value of 64%, and a negative predictive value 98%. At 24 hours, sensitivity was 100%, specificity 98%, positive predictive value 71%, and negative predictive value 100%. CONCLUSIONS: A positive dipstick seems to identify PEP cases and a negative test excludes PEP with high accuracy.

Transpancreatic biliary sphincterotomy for biliary access is safe also on a long-term scale.

BACKGROUND: Transpancreatic biliary sphincterotomy (TPBS) is an advanced cannulation method for accessing common bile duct (CBD) in endoscopic retrograde cholangiopancreatography (ERCP). If CBD cannulation is difficult, an endoscopist can open the septum between the pancreatic and biliary duct with a sphincterotome to gain access. Long-term results of this procedure are unclear. We wanted to evaluate the short- and long-term complications of TPBS on patients with native papilla and benign indication for ERCP. PATIENTS AND METHODS: ERCPs performed in Helsinki University Hospital between 2007 and 2013 were reviewed. The study group comprised 143 consecutive patients with TPBS and 140 controls (CG). Data were collected from patient records and a phone survey was performed as a follow-up ≥ 4 years after the index ERCP. RESULTS: Post-ERCP pancreatitis (PEP) developed in seven patients (4.9%) in TPBS and one patient (0.7%) in CG (p = 0.067). The rates of other acute complications were similar between the groups. ERCP ended with no access to CBD in four cases (2.8%) in TPBS. The median length of follow-up was 6 years in TPBS and 7 years in CG. During this period, three patients (2.1%) in TPBS and six patients (4.3%) in CG suffered from acute pancreatitis (AP) (p = 0.238). One (0.7%) patient in CG and none in TPBS developed chronic pancreatitis (CP). Abdominal pain was suffered by ten patients (6.9%) in TPBS and twelve patients (8.6%) in CG daily, whereas by six patients (4.2%) in TPBS and twelve patients (8.6%) in CG weekly. CONCLUSION: TPBS is a useful procedure, with acceptable complication rates. No significant difference occurred between the groups when evaluating the short-term or long-term complications with a follow-up period of four to 10 years. Additionally, no significant differences occurred in upper abdominal pain, episodes of AP, or development of CP.

Chronic use of statins and acetylsalicylic acid and incidence of post-endoscopic retrograde cholangiopancreatography acute pancreatitis: A multicenter, prospective, cohort study.

OBJECTIVES: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP. METHODS: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated. RESULTS: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors. CONCLUSIONS: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.

Association between chronic pancreatitis and pancreatic cancer: A 10-year retrospective study of endoscopically treated and surgical patients.

Pancreatic cancer (PC) has a poor prognosis. Chronic pancreatitis (CP) associates with high morbidity and mortality, and serves as a risk factor for PC. Our study aimed to assess the association between endoscopically treated CP patients and PC, and to establish the rate of CP among patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC). We retrospectively analyzed 458 CP patients undergoing endoscopic treatment (ET) between 2000 and 2010 and 349 PDAC patients undergoing pancreatic resection between 2000 and 2014 at the Helsinki University Hospital. The likelihood of diagnosing PC was highest within 2 years of a CP diagnosis: 21 of 30 PC diagnoses occurred during this time. After 2 years follow-up: 9 of 30 PC diagnoses occurred 2-12 years from CP diagnosis. Two patients were diagnosed with CP before PDAC. Multivariate analysis showed two prognostic factors indicative of PC development: biliary stricture (HR 9.21; 95% CI 3.76-22.08) and a higher age (per 5-year increases) at CP onset (HR 1.55; 95% CI 1.30-1.85). Among 458 CP patients, the median overall survival without PC was 14.7 years (95% CI 12.0-17.3), falling to 1.6 years (95% CI 1.2-2.0) with PC. The high incidence of PC among CP patients at the beginning of follow-up likely reflected an initially missed PC diagnoses. In long-term follow-up, an increasing PC incidence might reflect the PC-predisposing impact of CP. Thus, we recommend careful follow-up for patients presenting with a recently diagnosed CP and risk factors for PC.

Benign biliary strictures treated with biodegradable stents in patients with surgically altered anatomy using double balloon enteroscopy.

OBJECTIVES: Surgically altered anatomy complicates endoscopical procedures of pancreatobiliary tree. Biliary or hepaticojejunal anastomosis strictures have been managed using percutaneous transhepatic or double balloon enteroscopy (DBE) techniques with multiple plastic stents, or fully covered self-expandable metal stents. We report the first seven cases with surgically altered anatomy treated with biodegradable stents with DBE. MATERIALS AND METHODS: Seven cases with altered anatomy, all with Roux-en-Y hepaticojejunostomy (HJ), were treated for HJ anastomosis strictures (3 cases) and intrahepatic biliary stricture (4 cases). Fujifilm DB enteroscope with a 200 cm long and 3.2 mm wide working channel was used. Balloon dilatations were first performed and then 1-3 biodegradable stents were deployed with a pusher over a guidewire. RESULTS: Two patients had HJ due to liver resections, one due to biliary injury in cholecystectomy and four due to liver transplantation because of primary sclerosing cholangitis (PSC). Median duration of the procedures was 56 min. Deployment of the stents took less than 20 min per patient. There were no stent or cholangiography related adverse events, but one patient required endotracheal intubation for nose bleeding caused by the placement of nasopharyngeal tube. Two PSC patients had recurrent cholangitis in the follow up. There was one stent migration in 90 day follow up. With all the HJ anastomotic strictures resolution of strictures seemed to be achieved. CONCLUSIONS: Treatment of biliary or anastomosis strictures in altered anatomy is complex and time consuming. The biodegradable stent, which can be passed through working channel of a long enteroscope, seems promising in the treatment of these strictures. The benefit is that no stent removal is needed.

Doxapram as an additive to propofol sedation for endoscopic retrograde cholangiopancreatography: a placebo-controlled, randomized, double-blinded study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) requires moderate to deep sedation, usually with propofol. Adverse effects of propofol sedation are relatively common, such as respiratory and cardiovascular depression. This study was conducted to determine if doxapram, a respiratory stimulant, could be used to reduce the incidence of respiratory depression. METHODS: This is a single-center, prospective randomized double-blind study performed in the endoscopy unit of Helsinki University Central Hospital. 56 patients were randomized in a 1:1 ratio to either receive doxapram as an initial 1 mg/kg bolus and an infusion of 1 mg/kg/h (group DOX) or placebo (group P) during propofol sedation for ERCP. Main outcome measures were apneic episodes and hypoxemia (SpO2 < 90%). Mann-Whitney test for continuous variables and Fisher's exact test for discrete variables were used and mixed effects modeling to take into account repeated measurements on the same subject and comparing both changes within a group as a function of time and between the groups. RESULTS: There were no statistically significant differences in apneic episodes (p = 0.18) or hypoxemia (p = 0.53) between the groups. There was a statistically significant rise in etCO2 levels in both groups, but the rise was smaller in group P. There was a statistically significant rise in Bispectral Index (p = 0.002) but not modified Observer's Assessment of Agitation/Sedation (p = 0.21) in group P. There were no statistically significant differences in any other measured parameters. CONCLUSIONS: Doxapram was not effective in reducing respiratory depression caused by deep propofol sedation during ERCP. Further studies are warranted using different sedation protocols and dosing regimens. Clinical trial registration ClinicalTrials.gov ID NCT02171910.

Fully covered self-expanding metal stents for benign refractory pancreatic duct strictures in chronic pancreatitis.

Background: Pancreatic duct (PD) stricture is a common adverse event in chronic pancreatitis (CP). Primary treatment for refractory PD strictures is endotherapy (ET), including the insertion of multiple plastic stents. In addition, fully covered self-expandable metal stents (FC-SEMSs) have also been successfully used. More long-term studies are necessary to clarify the complication rate and efficiency, however. Methods: This retrospective study was comprised of 17 patients with symptomatic CP and refractory fibrotic main pancreatic duct (MPD) stricture treated with FC-SEMSs between 2010-2018 at the Helsinki University Hospital. Treated strictures were located in the pancreatic head. Technical success was defined as the accurate positioning of the stent and resolution of the MPD stricture. Clinical success was defined as pain relief at the end of the follow-up. Results: In 12 patients (71%), stricture resolution was accomplished. Clinical success was achieved in 12 patients (71%). The median duration of stenting was 169 days (range 15-804). Ten patients (58.8%) underwent a follow-up of two years or more. Early complications (≤7 days) occurred in two patients (12%): one pancreatitis and one cholestasis. Late complications (≥7 days) included severe abdominal pain (n = 2, 12%), pancreatitis (n = 3, 18%), cholestasis (n = 1, 6%) and stent migration (n = 7, 35%). Significant differences in stricture resolution and pain improvement were evident in patients with stent migration compared to patients without stent migration [1(14.3%) vs. 11(84.6%), p = .004 and 2(28.6%) vs. 11(84.6%), p = .022]. Conclusion: FC-SEMS placement is a safe and potentially effective treatment for this challenging group of patients. However, stent migration appears to affect the clinical and technical outcome.

Transcatheter arterial embolization in hepatic tumor hemorrhage.

Objective: Spontaneous hepatic tumor hemorrhage is a rare but challenging emergency especially among cirrhotic patients with poor hepatic function. This study aimed at analyzing the safety, efficacy and feasibility of transcatheter arterial embolization (TAE) in the treatment of hepatic tumor hemorrhage. Methods: This retrospective study included all patients undergoing embolization attempt for hepatic tumor hemorrhage in the Helsinki University Hospital during 2004-2017. Electronic medical records provided the study data. Outcomes included the 30-day rebleeding, complication and mortality rates, need for blood transfusions, durations of intensive care unit and hospital admissions, estimates of overall survival, and analysis of factors associated with 30-day mortality. Results: During the study period, 49 patients underwent angiography for hepatic tumor hemorrhage. TAE was technically feasible in 45 patients (92%), and controlled the bleeding with the first attempt in 84%. The 30-day complication and mortality rates were 57 and 33%, respectively. Major complications occurred in 33% of patients. In-hospital mortality was higher among cirrhotic than non-cirrhotic patients (55 versus 7%, p < .001). Patients with bleeding hepatic metastases, but no cirrhosis, had an in-hospital mortality of 0% with no major complications. Patients with benign etiology had a good prognosis and no bleeding- or tumor-related mortality. Discussion: TAE is an effective method in controlling the bleeding in spontaneous hepatic hemorrhage. Underlying pathology determines the prognosis that is poor especially in cirrhotic patients with bleeding hepatocellular carcinoma.

Assessment of sedation level for endoscopic retrograde cholangiopancreatography - a prospective validation study.

BACKGROUND AND AIMS: There is no consensus on how to assess the depth of sedation for endoscopic retrograde cholangiopancreatography (ERCP). This study was carried out in order to evaluate different methods of assessment of depth of sedation: bispectral index (BiS), modified Richmond Agitation/Sedation Scale (mRASS), modified Ramsay Sedation Scale (mRSS) and modified Observer Assessment of Alertness and Sedation (mOAAS) and their applicability to clinical practice. METHODS: Two hundred patients were recruited. Sedation was given by standard clinical practice using propofol sedation or patient controlled sedation. Sedation was assessed on all patients using the above-mentioned methods. BiS was considered the reference point for sedation scales. Cronbach's alpha was calculated to determine the consistency of different scales in respect to each other and prediction probability and Spearman's correlation coefficients of sedation scales were calculated to show the relationship between sedation scales and BiS. RESULTS: All scales showed high reliability with overall Cronbach's alpha 0.943. Dropping scales suggested better consistency between mOAAS, mRSS and mRASS than with BiS. Spearman's correlation and prediction probability showed similar results with all tested scales: mOAAS (0.695, 0.739), mRSS (0.673, 0.735), mRASS (0.683, 0.738), p < .01 for all scales. CONCLUSIONS: All tested methods were found to be reliable in the assessment of the depth of sedation when compared with each other. However, mRASS, mRSS and mOAAS require the patient to respond to verbal or tactile stimulus, which may impair execution of ERCP, whereas BiS information is collected directly from electroencephalogram and thus may be preferable in clinical setting.

Endoscopic Therapy of Biliary Injury After Cholecystectomy.

BACKGROUND: Iatrogenic bile duct injury (BDI) is a common complication after cholecystectomy. Patients are mainly treated endoscopically, but the optimal treatment method has remained unclear. AIMS: The aim was to analyze endoscopic treatment in BDI after cholecystectomy and to explore endoscopic sphincterotomy (ES), with or without stenting, as the primary treatment for an Amsterdam type A bile leak. METHODS: All patients referred to Helsinki University Hospital endoscopy unit due to a suspected BDI between the years 2004 and 2014 were included in this retrospective study. To collect the data, all ERC reports were reviewed. RESULTS: Of the 99 BDI patients, 94 (95%) had bile leak of whom 11 had concomitant stricture. Ninety-three percent of all patients were treated endoscopically. Seventy-one patients had native papillae and a leak in the cystic duct or peripheral radicals. They were treated with ES (ES group, n = 50) or with sphincterotomy and stenting (EST group, n = 21). There was no difference between the closure time of the fistula (p = 0.179), in the time of discharge from hospital (p = 0.298), or in the primary healing rate between the ES group and the EST group (45/50 vs 19/21 patients, p = 0.951). CONCLUSION: After the right patient selection, the success rate of endoscopic treatment can approach 100% for Amsterdam type A bile leak. ES is an effective and cost-effective single procedure with success rate similar to EST. It may be considered as a first-line therapy for the management of Amsterdam type A leaks.

Multiple plastic stents versus covered metal stent for treatment of anastomotic biliary strictures after liver transplantation: a prospective, randomized, multicenter trial.

BACKGROUND AND AIMS: Treatment of anastomotic biliary strictures (ABSs) after orthotopic liver transplantation by endoscopic insertion of multiple plastic stents (MPSs) is well established. The use of covered self-expandable metal stents (cSEMSs) for this indication is less investigated. METHODS: In an open-label, multicenter, randomized trial, patients with confirmed ABSs were randomly assigned 1:1 to receive either an MPS or a cSEMS. The primary endpoint was the number of endoscopic interventions until ABS resolution. Secondary endpoints were frequency of adverse events, treatment success rates, and time to treatment success and recurrence of ABS during follow-up of at least 1 year. RESULTS: Fifty-eight patients were included between 2012 and 2015, and 48 patients completed follow-up. Patients receiving MPS (n = 24) underwent a median of 4 (range, 3-12) endoscopic retrograde cholangiography examinations, whereas those in the cSEMS group (n = 24) underwent a median of 2 (range, 2-12) sessions until ABS resolution (P < .001). A median of 8 (range, 2-32) stents was used until ABS resolution within the MPS group and 1 (range, 1-24) in the cSEMS group (P < .0001). cSEMS migration occurred in 8 (33.3%) patients. Treatment duration did not differ significantly. Initial treatment success rates were high with 23 (95.8%) in the MPS group and 24 (100%) for cSEMSs (P = 1). Five (20.8%) patients in both groups showed stricture recurrence after a median follow-up of 500 days (range, 48-1317 days). CONCLUSIONS: cSEMSs for treatment of ABSs needed less endoscopic interventions to achieve similar efficacy as MPS and might become a new treatment standard. However, the optimal duration of cSEMS therapy and cost-efficacy have to be evaluated. (Clinical trial registration number: NCT01393067.).